Treatment of Relapsed or Refractory Acute Myeloblastic Leukemia
|ClinicalTrials.gov Identifier: NCT01435343|
Recruitment Status : Completed
First Posted : September 16, 2011
Last Update Posted : April 25, 2017
|First Submitted Date ICMJE||September 14, 2011|
|First Posted Date ICMJE||September 16, 2011|
|Last Update Posted Date||April 25, 2017|
|Start Date ICMJE||July 2012|
|Primary Completion Date||May 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Efficacy in terms of number of complete responses [ Time Frame: 1 year ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01435343 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Safety in terms of percentages of adverse events presented [ Time Frame: 1 year ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Treatment of Relapsed or Refractory Acute Myeloblastic Leukemia|
|Official Title ICMJE||Multicenter, Prospective, Open-label, Single-arm, Phase I-II Clinical Trial to Analyze Induction Therapy With a Combination of Fludarabine, Idarubicin, Cytarabine, G-CSF and Plerixafor for the Treatment of Young Patients With Relapsed or Refractory AML|
|Brief Summary||Second-line induction therapy with fludarabine, idarubicin, cytarabine,Granulocyte colony-stimulating factor (G-CSF) and plerixafor, in patients with relapsed or refractory Acute Myeloblastic Leukemia (AML) aged 65 or younger.|
This protocol corresponds to a multicenter, open-label, non-randomized, Phase I-II study designed to determine the safety and efficacy of the combination of plerixafor with chemotherapy in young patients with relapsed or refractory AML.
The clinical trial is divided into pre-treatment and treatment periods (induction and consolidation cycle(s) and consists of two general phases: an initial Phase I in which escalating doses of plerixafor will be given to 4 groups, each with 3 patients; and a secondary Phase II in which an additional patient group will be treated with the maximum tolerated dose (MTD) from Phase I.
In the pre-treatment period, all patients who provide written informed consent will be screened and any patients who meet all the inclusion and none of the exclusion criteria will be eligible for treatment.
The patients who are finally included in the study should begin treatment within 7 days after signing the informed consent document (ICD). The pre-treatment period begins when the ICD is signed and enrollment occurs when the patient receives the first study drug of the treatment regimen (i.e., Day 1 of the induction cycle).
In this study, the induction cycle will consist of fludarabine 30 mg/m2/day intravenously on days 1 to 4, idarubicin 10 mg/m2/day intravenously on days 1 to 3, cytarabine 2 g/m2/day intravenously on days 1 to 4, G-CSF 5 μg/kg/day subcutaneously from days 1 to 4, and plerixafor intravenously from days 1 to 4. The dose of plerixafor will be escalated over 4 groups of three patients as follows: 240 μg/kg/day (120 μg/kg/12 h); 320 μg/kg/day (160 μg/kg/12 h); 400 μg/kg/day (200 μg/kg/12 h); and 480 μg/kg/day (240 μg/kg/12 h). If MTD is observed with the first treatment dose of plerixafor the dose will be progressively deescalated to 160 μg/kg/day (80μg/kg/12 h) on a first deescalating level or 240 μg/kg/day in a single daily dose on a second deescalating level if no twice a day (BID) dose is tolerated. Patient enrollment will be expanded to a total of 55 patients using MTD. If patients do not achieve CR after one induction cycle they will leave the study and be followed according to routine clinical practice. Patients who achieve complete response (CR) who are eligible for allogeneic hematopoietic stem cell transplantation (HSCT) and have a donor will leave the trial and receive allogeneic HSCT and will be followed according to routine clinical practice. Patients who achieve CR and are not eligible for allogeneic HSCT or do not have a donor will receive two consolidations with cytarabine at 3 g/m2/12 hours on days 1, 3 and 5 along with Granulocyte colony-stimulating factor (GCSF) at 5 μg/kg/day on days 1 to 5 and plerixafor at the same dose used in the induction cycle on days 1, 3 and 5, coinciding with the days that cytarabine is administered.
In the context of this protocol, a treatment cycle is defined as the first day of the study drug administration regimens (Day 1) up to and including the day before the first day of the treatment cycle immediately afterwards. The treatment cycles will begin after Day 28 but no later than Day 85, counting from Day 1 of the treatment cycle immediately before.
Patients will be assessed in the three days before each cycle (see Appendix A). Follow-up, outside the protocol in routine clinical practice, will be performed monthly during the first year and at least every three months during the second year; notwithstanding, visits may be more frequent at the discretion of each site or based on the clinical characteristics.
All treatment cycles will be administered while the patient is hospitalized. Clinical procedures for the care of patients with acute leukemia require flexibility. However, deviations from the study treatment defined in this section must be prospectively discussed with the coordinator.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Acute Myeloblastic Leukemia|
|Study Arms||Not Provided|
|Publications *||Martínez-Cuadrón D, Boluda B, Martínez P, Bergua J, Rodríguez-Veiga R, Esteve J, Vives S, Serrano J, Vidriales B, Salamero O, Cordón L, Sempere A, Jiménez-Ubieto A, Prieto-Delgado J, Díaz-Beyá M, Garrido A, Benavente C, Pérez-Simón JA, Moscardó F, Sanz MA, Montesinos P; CETLAM and PETHEMA groups. A phase I-II study of plerixafor in combination with fludarabine, idarubicin, cytarabine, and G-CSF (PLERIFLAG regimen) for the treatment of patients with the first early-relapsed or refractory acute myeloid leukemia. Ann Hematol. 2018 Feb 2. doi: 10.1007/s00277-018-3229-5. [Epub ahead of print] Erratum in: Ann Hematol. 2018 Feb 23;:.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||December 2016|
|Primary Completion Date||May 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Total bilirubin <1.5 x Institutional Upper Limit of Normal (ULN); and AST and ALT <2.5 xULN; and Serum creatinine <1.0 mg/dL; if serum creatinine <1.0 mg/dL, then, the estimated glomerular filtration rate (GFR) must be <60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation - Minimal impairment of cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) >40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening >22% on echocardiography exam;
Total bilirubin > 1.5 x upper limit of normal (ULN) provided that this is not attributable to AML itself; or AST and ALT > 2.5 xULN provided that this is not attributable to AML itself; or Serum creatinine > 1.0 mg/dL provided that the estimated glomerular filtration rate (GFR) is ≤ 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation
- Impaired cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) < 40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening < 22% on echocardiography exam;
Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed
|Ages||18 Years to 65 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Spain|
|Removed Location Countries|
|NCT Number ICMJE||NCT01435343|
|Other Study ID Numbers ICMJE||PLERIFLAG|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||PETHEMA Foundation|
|Study Sponsor ICMJE||PETHEMA Foundation|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||PETHEMA Foundation|
|Verification Date||September 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP